• Dysfunction of the central serotonergic system has been variously associated with depression and with suicidal and/or impulsive aggressive behavior. To evaluate central serotonergic function in relation to these variables, prolactin responses to a singledose challenge with fenfluramine hydrochloride (60 mg orally), a serotonin releasing/uptake-inhibiting agent, were examined in 45 male patients with clearly defined major affective (n = 25) and/or personality disorder (n 20) and in 18 normal male control patients. Prolactin responses to fenfluramine among all patients were reduced compared with responses of controls. Reduced prolactin responses to fenfluramine were correlated with history of suicide attempt in all patients but with clinician and selfreported ratings of impulsive aggression in patients with personality disorder only; there was no correlation with depression. These results suggest that reduced central serotonergic function is present in a subgroup of patients with major affective and/or personality disorder and is associated with history of suicide attempt in patients with either disorder, but with impulsive aggression in patients with personality disorder only.

Serotonergic Studies in Patients with Affective and Personality Disorders: Correlates with Suicidal and Impulsive Aggressive Behavior

I. Introduction THE STABILITY of the “milieu interieur” was first recognized by Claude Bernard (1), and this concept was extended by Walter Cannon (2), who coined the term homeostasis to denote the condition of relative constancy of the internal environment. The hypothalamic-pituitary-adrenal axis (HPA) and the autonomic nervous system are recognized as primary effector systems which serve to minimize excursions from the homeostatic state and to restore a relative equilibrium in response to disturbances (3, 4). Many of the physiological adjustments accompanying sympathetic activation complement those brought about by glucocorticoid secretion. Indeed, the responsiveness and physiological consequences of activation of these two systems are so inter-twined as to have generated the hypothesis that activation of the HPA is evoked by sympathoadrenomedullary activation (5, 6). Thus an organism's response to an actual or perceived challenge (stressor) usually involves activation of both the HPA and the sympatheti...

Catecholaminergic Modulation of Corticotropin-Releasing Factor and Adrenocorticotropin Secretion

The role of central serotonergic (5-HT) system dysfunction in the regulation of aggression in both animals and man has been investigated for more than the past two decades. Evidence for reduced central 5-HT in the mediation of aggression comes from both behavioural and correlative studies. Functional reduction and augmentation of 5-HT activity is respectively associated with increased and decreased aggression in various animal models of aggression. While similar studies in man have not been performed, strong and consistent associations between indices reflecting reduced pre-synaptic 5-HT activity and aggression have been reported. Evidence of post-synaptic receptor upregulation in the brains of suicide victims has also been reported leaving the functional status 5-HT activity in such patients an open question. However, reduced neuroendocrine (i.e. prolactin) responses to fenfluramine, a 5-HT uptake inhibitor/releaser, which activates both pre- and post-synaptic sides of the 5-HT synapse, strongly suggest that overall central 5-HT activity is reduced in mood and/or personality disorder patients with history of suicidal and/or impulsive aggressive behaviour. Preliminary data with the 5-HT receptor agonist m-chlorophenylpiperazine further suggest that reduced activity of post-synaptic 5-HT receptors may be an important correlate of impulsive aggressive behaviour. Pharmacological agents with potent 5-HT pre- and/or post-synaptic augmenting effects should be tested clinically to determine their efficacy in the treatment of impulsive aggressive behaviour in psychiatric patients.

Central serotonin and impulsive aggression.

Biology and Comparative Physiology of Birds

Restraint stress in biomedical research: A review

To investigate the role played by hypothalamic noradrenaline (NE) in the regulation of TRH-TSH release during tonic and cold activated conditions, drugs and surgical procedures able to interfere with central NE tonus were utilized. The time course of the effect of alpha-methyl-para-tyrosine (alpha-MpT) on basal TSH secretion was followed. The tyrosine hydroxylase (TH) inhibitor was unable to modify TSH plasma levels, whereas NE hypothalamic content decreased beginning with the third hour. The acute release of TSH evoked by cold exposure (CE) was prevented by pretreatment with alpha-MpT 1 h before; when alpha-MpT was followed 40 min later by clonidine, a central noradrenergic stimulating agent, TSH response to cold, previously blocked by the TH inhibitor was restored. Intraventricular injection of 10 micrograms of clonidine hydrochloride in unstimulated rats caused a significant rise of basal TSH levels 3, but not 10 min after the administration. Complex deafferentation of the medial basal hypothalamus (MBH), which destroys all the NE fibers afferent to this area, caused no change of thyrotropin secretion in basal conditions. Deafferented animals did not show any acute increase of TSH in response to CE. The results of this study provide evidence that NE may be the catecholamine (CA) mediating the rise in TSH following CE and that the direct stimulation of central NE receptors can evoke a massive TSH release from the anterior pituitary gland also in basal conditions.

P. Preziosi

Papers

The role of central noradrenergic neurons in the control of thyrotropin secretion in the rat.

Effect of midbrain raphe lesion or 5,7-dihydroxytryptamine treatment on the prolactin-releasing action of quipazine andd-fenfluramine in rats

Influence of restraint stress, corticosterone and betamethasone on brain amine levels

Effect of selective lesioning of serotonin-containing neurons on the TSH-inhibiting action of d-fenfluramine in male rats.

Effect of selective degeneration of brain serotonin-containing neurons on plasma corticosterone levels: studies with d-fenfluramine.